CED4_CAEEL
ID CED4_CAEEL Reviewed; 571 AA.
AC P30429; Q5BHI5;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Cell death protein 4;
GN Name=ced-4; ORFNames=C35D10.9;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=1286611; DOI=10.1242/dev.116.2.309;
RA Yuan J., Horvitz H.R.;
RT "The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein
RT and is expressed during the period of extensive programmed cell death.";
RL Development 116:309-320(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RX PubMed=3955651; DOI=10.1016/0092-8674(86)90004-8;
RA Ellis H.M., Horvitz H.R.;
RT "Genetic control of programmed cell death in the nematode C. elegans.";
RL Cell 44:817-829(1986).
RN [4]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=8706125; DOI=10.1016/s0092-8674(00)80092-6;
RA Shaham S., Horvitz H.R.;
RT "An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death
RT inhibitor.";
RL Cell 86:201-208(1996).
RN [5]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH CED-9.
RX PubMed=9027313; DOI=10.1126/science.275.5303.1126;
RA Wu D., Wallen H.D., Nunez G.;
RT "Interaction and regulation of subcellular localization of CED-4 by CED-
RT 9.";
RL Science 275:1126-1129(1997).
RN [6]
RP FUNCTION.
RX PubMed=9927601; DOI=10.1242/dev.126.5.1011;
RA Gumienny T.L., Lambie E., Hartwieg E., Horvitz H.R., Hengartner M.O.;
RT "Genetic control of programmed cell death in the Caenorhabditis elegans
RT hermaphrodite germline.";
RL Development 126:1011-1022(1999).
RN [7]
RP INTERACTION WITH MAC-1, AND MUTAGENESIS OF ILE-280.
RX PubMed=10101135; DOI=10.1242/dev.126.9.2021;
RA Wu D., Chen P.J., Chen S., Hu Y., Nunez G., Ellis R.E.;
RT "C. elegans MAC-1, an essential member of the AAA family of ATPases, can
RT bind CED-4 and prevent cell death.";
RL Development 126:2021-2031(1999).
RN [8]
RP FUNCTION, AND INTERACTION WITH FEM-1.
RX PubMed=10764728; DOI=10.1074/jbc.c000146200;
RA Chan S.L., Yee K.S., Tan K.M., Yu V.C.;
RT "The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3
RT substrate that associates with CED-4 and mediates apoptosis in mammalian
RT cells.";
RL J. Biol. Chem. 275:17925-17928(2000).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10688797; DOI=10.1126/science.287.5457.1485;
RA Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y.,
RA Horvitz H.R.;
RT "Translocation of C. elegans CED-4 to nuclear membranes during programmed
RT cell death.";
RL Science 287:1485-1489(2000).
RN [10]
RP FUNCTION.
RX PubMed=11226309; DOI=10.1073/pnas.041613098;
RA Aballay A., Ausubel F.M.;
RT "Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis
RT elegans from Salmonella typhimurium-mediated killing.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2735-2739(2001).
RN [11]
RP MUTAGENESIS OF 80-GLN--CYS-571.
RX PubMed=12944970; DOI=10.1038/nature01920;
RA Bloss T.A., Witze E.S., Rothman J.H.;
RT "Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in
RT Caenorhabditis elegans.";
RL Nature 424:1066-1071(2003).
RN [12]
RP FUNCTION, AND INTERACTION WITH CED-9.
RX PubMed=15383288; DOI=10.1016/j.molcel.2004.08.022;
RA Yan N., Gu L., Kokel D., Chai J., Li W., Han A., Chen L., Xue D., Shi Y.;
RT "Structural, biochemical, and functional analyses of CED-9 recognition by
RT the proapoptotic proteins EGL-1 and CED-4.";
RL Mol. Cell 15:999-1006(2004).
RN [13]
RP FUNCTION.
RX PubMed=17329362; DOI=10.1242/dev.02818;
RA Maurer C.W., Chiorazzi M., Shaham S.;
RT "Timing of the onset of a developmental cell death is controlled by
RT transcriptional induction of the C. elegans ced-3 caspase-encoding gene.";
RL Development 134:1357-1368(2007).
RN [14]
RP FUNCTION.
RX PubMed=21901106; DOI=10.1371/journal.pgen.1002238;
RA Rutkowski R., Dickinson R., Stewart G., Craig A., Schimpl M., Keyse S.M.,
RA Gartner A.;
RT "Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell
RT apoptosis by Ras/MAPK signaling.";
RL PLoS Genet. 7:E1002238-E1002238(2011).
RN [15]
RP FUNCTION.
RX PubMed=22629231; DOI=10.1371/journal.pbio.1001331;
RA Pinan-Lucarre B., Gabel C.V., Reina C.P., Hulme S.E., Shevkoplyas S.S.,
RA Slone R.D., Xue J., Qiao Y., Weisberg S., Roodhouse K., Sun L.,
RA Whitesides G.M., Samuel A., Driscoll M.;
RT "The core apoptotic executioner proteins CED-3 and CED-4 promote initiation
RT of neuronal regeneration in Caenorhabditis elegans.";
RL PLoS Biol. 10:E1001331-E1001331(2012).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23106139; DOI=10.1111/jnc.12072;
RA VanDuyn N., Settivari R., LeVora J., Zhou S., Unrine J., Nass R.;
RT "The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine
RT neuron degeneration.";
RL J. Neurochem. 124:147-157(2013).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25432023; DOI=10.7554/elife.04265;
RA Weaver B.P., Zabinsky R., Weaver Y.M., Lee E.S., Xue D., Han M.;
RT "CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression
RT dynamics for robust development in C. elegans.";
RL Elife 3:E04265-E04265(2014).
RN [18]
RP FUNCTION.
RX PubMed=26074078; DOI=10.1016/j.celrep.2015.05.031;
RA Meng L., Mulcahy B., Cook S.J., Neubauer M., Wan A., Jin Y., Yan D.;
RT "The cell death pathway regulates synapse elimination through cleavage of
RT gelsolin in Caenorhabditis elegans neurons.";
RL Cell Rep. 11:1737-1748(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF ISOFORM A IN COMPLEX WITH ATP;
RP MAGNESIUM AND CED-9, FUNCTION, AND MUTAGENESIS OF VAL-252; ARG-255; MET-256
RP AND 272-ASP-ASP-273.
RX PubMed=16208361; DOI=10.1038/nature04002;
RA Yan N., Chai J., Lee E.S., Gu L., Liu Q., He J., Wu J.W., Kokel D., Li H.,
RA Hao Q., Xue D., Shi Y.;
RT "Structure of the CED-4-CED-9 complex provides insights into programmed
RT cell death in Caenorhabditis elegans.";
RL Nature 437:831-837(2005).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.53 ANGSTROMS) IN COMPLEX WITH CED-3; MAGNESIUM AND
RP ATP, AND FUNCTION.
RX PubMed=20434985; DOI=10.1016/j.cell.2010.03.017;
RA Qi S., Pang Y., Hu Q., Liu Q., Li H., Zhou Y., He T., Liang Q., Liu Y.,
RA Yuan X., Luo G., Li H., Wang J., Yan N., Shi Y.;
RT "Crystal structure of the Caenorhabditis elegans apoptosome reveals an
RT octameric assembly of CED-4.";
RL Cell 141:446-457(2010).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) IN COMPLEX WITH CED-3 AND ATP
RP (ISOFORM A), FUNCTION, AND MUTAGENESIS OF ALA-416.
RX PubMed=24065769; DOI=10.1101/gad.224428.113;
RA Huang W., Jiang T., Choi W., Qi S., Pang Y., Hu Q., Xu Y., Gong X.,
RA Jeffrey P.D., Wang J., Shi Y.;
RT "Mechanistic insights into CED-4-mediated activation of CED-3.";
RL Genes Dev. 27:2039-2048(2013).
CC -!- FUNCTION: Component of the egl-1, ced-9, ced-4 and ced-3 apoptotic
CC signaling cascade required for the initiation of programmed cell death
CC in cells fated to die during embryonic and postembryonic development
CC (PubMed:3955651). During oogenesis, required for germline apoptosis
CC downstream of ced-9 and upstream of ced-3 but independently of egl-1
CC (PubMed:9927601). May regulate germline apoptosis in response to DNA
CC damage, probably downstream of let-60/ras and mpk-1 pathway
CC (PubMed:21901106). Regulates CEP neuron apoptosis in response to high
CC Al(3+) levels (PubMed:23106139). During male tail morphogenesis,
CC promotes apoptosis of the tail-spike cell upstream of ced-3 but
CC independently of egl-1 and ced-9 (PubMed:17329362). May play a role in
CC sex-specific cell apoptosis, probably by promoting ced-3-mediated
CC cleavage of sex-determining protein fem-1 (PubMed:10764728). During
CC larval development, required for the elimination of transient
CC presynaptic components downstream of egl-1 and ced-9 and upstream of
CC ced-3 apoptotic pathway (PubMed:26074078). Downstream of calreticulin
CC crt-1 and upstream of ced-3 and independently of egl-1 and ced-9, plays
CC a role in the initial steps of axonal regrowth following axotomy
CC (PubMed:22629231). Together with ain-1, a component of the miRNA-
CC induced-silencing complex (miRISC), and probably upstream of ced-3,
CC regulates temporal cell fate patterning during larval development
CC (PubMed:25432023). May play a role in resistance to S.typhimurium-
CC mediated infection (PubMed:11226309). {ECO:0000269|PubMed:10764728,
CC ECO:0000269|PubMed:11226309, ECO:0000269|PubMed:17329362,
CC ECO:0000269|PubMed:21901106, ECO:0000269|PubMed:22629231,
CC ECO:0000269|PubMed:23106139, ECO:0000269|PubMed:25432023,
CC ECO:0000269|PubMed:26074078, ECO:0000269|PubMed:3955651,
CC ECO:0000269|PubMed:9927601}.
CC -!- FUNCTION: [Isoform a]: Plays a major role in programmed cell death
CC (PubMed:1286611, PubMed:8706125). egl-1 binds to and directly inhibits
CC the activity of ced-9, releasing the cell death activator ced-4 from a
CC ced-9/ced-4 containing protein complex and allowing ced-4 to induce
CC caspase ced-3 autoproteolytic cleavage and activation (PubMed:15383288,
CC PubMed:16208361, PubMed:20434985, PubMed:24065769). Also forms a
CC holoenzyme with processed ced-3 enhancing ced-3 activity
CC (PubMed:20434985). {ECO:0000269|PubMed:10688797,
CC ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:15383288,
CC ECO:0000269|PubMed:16208361, ECO:0000269|PubMed:20434985,
CC ECO:0000269|PubMed:24065769, ECO:0000269|PubMed:8706125}.
CC -!- FUNCTION: [Isoform b]: Prevents programmed cell death.
CC {ECO:0000269|PubMed:8706125}.
CC -!- SUBUNIT: Associates as an asymmetric homodimer with ced-9
CC (PubMed:16208361, PubMed:9027313, PubMed:15383288). Upon release from
CC ced-9, forms an octamer, known as the apoptosome, and interacts with
CC ced-3; the interaction results in ced-3 autoproteolytic cleavage and
CC activation (PubMed:20434985, PubMed:24065769). The octamer (a tetramer
CC of an asymmetric dimer) also interacts with two processed ced-3 to form
CC a stable holoenzyme (PubMed:20434985). Interacts with sex-determining
CC protein fem-1 (PubMed:10764728). May form a complex composed of ced-3,
CC ced-4 and mac-1 or of ced-9, ced-4 and mac-1 (PubMed:10101135). Within
CC the complex, interacts with ced-4 (PubMed:10101135).
CC {ECO:0000269|PubMed:10101135, ECO:0000269|PubMed:10764728,
CC ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361,
CC ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769,
CC ECO:0000269|PubMed:9027313}.
CC -!- INTERACTION:
CC P30429; P42573: ced-3; NbExp=10; IntAct=EBI-494118, EBI-494247;
CC P30429; P41958: ced-9; NbExp=17; IntAct=EBI-494118, EBI-494110;
CC P30429; Q20924: sun-1; NbExp=3; IntAct=EBI-494118, EBI-15599048;
CC P30429-2; P42573: ced-3; NbExp=13; IntAct=EBI-536271, EBI-494247;
CC P30429-2; P41958: ced-9; NbExp=5; IntAct=EBI-536271, EBI-494110;
CC P30429-2; Q9NAG4: mac-1; NbExp=8; IntAct=EBI-536271, EBI-2005767;
CC P30429-2; Q07817-1: BCL2L1; Xeno; NbExp=2; IntAct=EBI-536271, EBI-287195;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10688797,
CC ECO:0000269|PubMed:9027313}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Note=In non
CC cell death induced cells, ced-9 is required for mitochondrial
CC localization. Perinuclear in cell death induced cells.
CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:C35D10.9b}; Synonyms=Long
CC {ECO:0000303|PubMed:8706125};
CC IsoId=P30429-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:C35D10.9a}; Synonyms=Short
CC {ECO:0000303|PubMed:8706125};
CC IsoId=P30429-2; Sequence=VSP_013199;
CC -!- DEVELOPMENTAL STAGE: Abundantly expressed during embryogenesis and to a
CC lesser extent in larvae and adults (PubMed:1286611). Expression starts
CC at the 100-cell stage and persists through embryogenesis (at protein
CC level) (PubMed:9027313). Not expressed in larvae and adults (at protein
CC level) (PubMed:9027313). {ECO:0000269|PubMed:1286611,
CC ECO:0000269|PubMed:9027313}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a block in almost all programmed
CC cell deaths that normally occur during development (PubMed:1286611).
CC RNAi-mediated knockdown causes a defect in egg laying in a small
CC proportion of animals (PubMed:25432023). Also causes a moderate
CC increase in CEP neuron survival in response to high Al(3+) levels
CC (PubMed:23106139). In an ain-1 mutant background, enhances the
CC proportion of animals arrested at the larval stage, with egg-laying
CC defects and with a ruptured vulva (PubMed:25432023).
CC {ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:23106139,
CC ECO:0000269|PubMed:25432023}.
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DR EMBL; X69016; CAA48781.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD66781.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD66782.1; -; Genomic_DNA.
DR PIR; S72566; S72566.
DR RefSeq; NP_001021202.1; NM_001026031.2. [P30429-2]
DR RefSeq; NP_001021203.1; NM_001026032.1. [P30429-1]
DR PDB; 2A5Y; X-ray; 2.60 A; B/C=1-571.
DR PDB; 3LQQ; X-ray; 3.53 A; A/B=1-571.
DR PDB; 3LQR; X-ray; 3.90 A; A/B=1-571.
DR PDB; 4M9S; X-ray; 3.21 A; A/B/C/D=1-571.
DR PDB; 4M9X; X-ray; 3.34 A; A/B=1-571.
DR PDB; 4M9Y; X-ray; 4.20 A; A/B=1-571.
DR PDB; 4M9Z; X-ray; 3.40 A; A/B/C/D=1-571.
DR PDBsum; 2A5Y; -.
DR PDBsum; 3LQQ; -.
DR PDBsum; 3LQR; -.
DR PDBsum; 4M9S; -.
DR PDBsum; 4M9X; -.
DR PDBsum; 4M9Y; -.
DR PDBsum; 4M9Z; -.
DR AlphaFoldDB; P30429; -.
DR SMR; P30429; -.
DR BioGRID; 40877; 17.
DR ComplexPortal; CPX-1358; ced-3-ced-4-mac-1 complex.
DR ComplexPortal; CPX-1359; ced-4-ced-9-mac-1 complex.
DR ComplexPortal; CPX-1360; ced-3-ced-4 caspase complex.
DR ComplexPortal; CPX-399; ced-9-ced-4 complex.
DR DIP; DIP-1016N; -.
DR IntAct; P30429; 7.
DR STRING; 6239.C35D10.9b; -.
DR EPD; P30429; -.
DR PaxDb; P30429; -.
DR PeptideAtlas; P30429; -.
DR PRIDE; P30429; -.
DR EnsemblMetazoa; C35D10.9a.1; C35D10.9a.1; WBGene00000418. [P30429-2]
DR EnsemblMetazoa; C35D10.9b.1; C35D10.9b.1; WBGene00000418. [P30429-1]
DR GeneID; 175643; -.
DR KEGG; cel:CELE_C35D10.9; -.
DR UCSC; C35D10.9b; c. elegans. [P30429-1]
DR CTD; 175643; -.
DR WormBase; C35D10.9a; CE01203; WBGene00000418; ced-4. [P30429-2]
DR WormBase; C35D10.9b; CE38154; WBGene00000418; ced-4. [P30429-1]
DR eggNOG; KOG4658; Eukaryota.
DR HOGENOM; CLU_496380_0_0_1; -.
DR InParanoid; P30429; -.
DR OMA; YYEHVIW; -.
DR OrthoDB; 1576724at2759; -.
DR PhylomeDB; P30429; -.
DR SignaLink; P30429; -.
DR EvolutionaryTrace; P30429; -.
DR PRO; PR:P30429; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000418; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0008303; C:caspase complex; IDA:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:WormBase.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IDA:WormBase.
DR GO; GO:0051432; F:BH1 domain binding; IPI:WormBase.
DR GO; GO:0051434; F:BH3 domain binding; IPI:WormBase.
DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0061133; F:endopeptidase activator activity; IDA:WormBase.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; IDA:WormBase.
DR GO; GO:0030042; P:actin filament depolymerization; IMP:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:0048598; P:embryonic morphogenesis; IGI:WormBase.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IMP:ComplexPortal.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:WormBase.
DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:WormBase.
DR GO; GO:0010954; P:positive regulation of protein processing; IDA:UniProtKB.
DR GO; GO:1905808; P:positive regulation of synapse pruning; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0008361; P:regulation of cell size; IGI:WormBase.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:WormBase.
DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IGI:UniProtKB.
DR DisProt; DP03045; -. [P30429-2]
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR016854; Apop_reg_Ced-4.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002182; NB-ARC.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF00931; NB-ARC; 1.
DR PIRSF; PIRSF027202; Apop_reg_Ced-4; 1.
DR SMART; SM00114; CARD; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm;
KW Magnesium; Metal-binding; Mitochondrion; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..571
FT /note="Cell death protein 4"
FT /id="PRO_0000089470"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 133..439
FT /note="NB-ARC"
FT /evidence="ECO:0000255"
FT BINDING 131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:16208361,
FT ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769,
FT ECO:0007744|PDB:2A5Y, ECO:0007744|PDB:3LQQ,
FT ECO:0007744|PDB:3LQR, ECO:0007744|PDB:4M9S,
FT ECO:0007744|PDB:4M9X, ECO:0007744|PDB:4M9Y,
FT ECO:0007744|PDB:4M9Z"
FT BINDING 162..167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:16208361,
FT ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769,
FT ECO:0007744|PDB:2A5Y, ECO:0007744|PDB:3LQQ,
FT ECO:0007744|PDB:3LQR, ECO:0007744|PDB:4M9S,
FT ECO:0007744|PDB:4M9X, ECO:0007744|PDB:4M9Y,
FT ECO:0007744|PDB:4M9Z"
FT BINDING 166
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16208361,
FT ECO:0000269|PubMed:20434985"
FT BINDING 171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24065769,
FT ECO:0007744|PDB:4M9S"
FT VAR_SEQ 212..234
FT /note="ARVVSDTDDSHSITDFINRVLSR -> K (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_013199"
FT MUTAGEN 80..571
FT /note="Missing: In n1162; reduces the number of apoptotic
FT corpses and restores the number of male tail rays in an
FT icd-1 RNAi background."
FT /evidence="ECO:0000269|PubMed:12944970"
FT MUTAGEN 252
FT /note="V->D: Loss of dimerization without affecting
FT interaction with ced-9, loss of ced-3 activation and severe
FT reduction in the number of cell corpses in embryos in a
FT ced-1 mutant background; when associated with E-255 and E-
FT 256."
FT /evidence="ECO:0000269|PubMed:16208361"
FT MUTAGEN 255
FT /note="R->E: Severe reduction in the number of cell corpses
FT in embryos in a ced-1 mutant background. Loss of
FT dimerization without affecting interaction with ced-9, loss
FT of ced-3 activation and severe reduction in the number of
FT cell corpses in embryos in a ced-1 mutant background; when
FT associated with E-252 and E-256."
FT /evidence="ECO:0000269|PubMed:16208361"
FT MUTAGEN 256
FT /note="M->E: Loss of dimerization without affecting
FT interaction with ced-9, loss of ced-3 activation and severe
FT reduction in the number of cell corpses in embryos in a
FT ced-1 mutant background; when associated with E-252 and E-
FT 255."
FT /evidence="ECO:0000269|PubMed:16208361"
FT MUTAGEN 272..273
FT /note="DD->AA: Severe reduction in the number of cell
FT corpses in embryos in a ced-1 mutant background."
FT /evidence="ECO:0000269|PubMed:16208361"
FT MUTAGEN 280
FT /note="I->N: In n1948; no effect on the interaction with
FT mac-1."
FT /evidence="ECO:0000269|PubMed:10101135"
FT MUTAGEN 416
FT /note="A->W: Reduced interaction with ced-3."
FT /evidence="ECO:0000269|PubMed:24065769"
FT HELIX 4..20
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 27..32
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 38..45
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 50..64
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 69..77
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 81..96
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 105..108
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:4M9X"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:4M9S"
FT HELIX 250..261
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 267..274
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 277..285
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 289..296
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 297..302
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 317..326
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 336..348
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 352..359
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 367..380
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 381..384
FT /evidence="ECO:0007829|PDB:4M9S"
FT STRAND 389..395
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 396..405
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 409..414
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 429..435
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 450..458
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 466..469
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 480..487
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 493..499
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:2A5Y"
FT TURN 510..512
FT /evidence="ECO:0007829|PDB:4M9Z"
FT HELIX 555..558
FT /evidence="ECO:0007829|PDB:4M9S"
FT HELIX 559..562
FT /evidence="ECO:0007829|PDB:2A5Y"
SQ SEQUENCE 571 AA; 65336 MW; 6BE9893946B79E6C CRC64;
MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI
YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL
LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI
GINYDSIVWL KDSGTAPKST FDLFTDILLM LARVVSDTDD SHSITDFINR VLSRSEDDLL
NFPSVEHVTS VVLKRMICNA LIDRPNTLFV FDDVVQEETI RWAQELRLRC LVTTRDVEIS
NAASQTCEFI EVTSLEIDEC YDFLEAYGMP MPVGEKEEDV LNKTIELSSG NPATLMMFFK
SCEPKTFEKM AQLNNKLESR GLVGVECITP YSYKSLAMAL QRCVEVLSDE DRSALAFAVV
MPPGVDIPVK LWSCVIPVDI CSNEEEQLDD EVADRLKRLS KRGALLSGKR MPVLTFKIDH
IIHMFLKHVV DAQTIANGIS ILEQRLLEIG NNNVSVPERH IPSHFQKFRR SSASEMYPKT
TEETVIRPED FPKFMQLHQK FYDSLKNFAC C
